Devices for the automated release of liquid medicaments normally are used with patients who have a continuous need for a medicine that can be administered by subcutaneous infusion, which need can vary in the course of a day. Example applications for computer-controlled infusion pump devices, such as insulin pumps, include certain pain therapies and the treatment of diabetes. Such devices can be carried by a patient on the body and can contain a certain amount of liquid medicament in a medicine reservoir in the form of a container. The medicine reservoir often comprises medicine sufficient for one or several days. The liquid medicament is supplied to the patient's body from the medicine reservoir through an infusion cannula or an injection needle.
Convenience and discretion are paramount concerns for patients who may self-administer medicaments, for example, insulin, by means such as an infusion pump. Consequently, the dimensions of such infusion devices must be limited, and particularly the overall length, width and thickness should be as small as possible to prevent the devices from being evident through clothing and to allow the patient to carry the devices as comfortably as possible.
In the interest of maintaining sterility and preventing contamination, typically the devices are single-use devices. The devices may be delivered pre-filled with a certain liquid medicament, or empty, ready to be filled. This self-filling of containers has the advantage that medicaments that are not readily available in pre-filled containers can be used for such infusion pump devices, thereby providing the patient with a larger choice of sources for delivery of the medicaments. Alternatively, devices or parts of the devices can be reused by the patient, for example, by replacing an empty medicament container or by refilling the container.
Standard infusion pump devices that are carried on or near the body have a medicine reservoir with a cylindrical ampoule and a displacement piston. The piston is pushed into the ampoule by a piston rod or a threaded spindle to convey the liquid medicament. These known designs are undesirably long or thick and do not provide advantageously compact infusion pumps.
Manufacturers try to meet the demand of small infusion pump devices by various means. For example, the infusion pump can be divided into structural assemblies arranged in separate, smaller, housings that can be joined by a wireless or a wired connection. An example of such a modular infusion pump device is disclosed in US 2006/0184119 A1.
Another possibility is the use of particularly flat construction containers. For example, the cylindrical ampoule may be replaced by a container having a rectangular or other suitable cross-section and may interact with a displacement piston of a corresponding shape. Different embodiments of such compact medicine reservoir devices are shown in WO 2008/122135 A1.
A further approach to reduce the overall volume of an infusion device is to replace the syringe-type dosing mechanism with a downstream pump system. In the syringe-type dosing mechanism, an actuator displaces a piston along a long axis of a container to convey the appropriate amount of liquid medicine. In the device with a downstream pump system, a miniaturized pump downstream of the reservoir causes a suction pressure that conveys the product from the reservoir to its destination. An example of such a pump is described in WO 2004/009162 A1.
For some of the above mentioned infusion devices, the suction pressure achievable with the pump system is not very high. A suitable container for such devices is disclosed in US 2007/0123820 A1, comprising a flat container and a flat piston body arranged in the body in a sliding manner. Fully filled, such a container has a ratio of maximum height to overall width of less than 1.25. The cross-sectional area of the container in relation to the displacement axis is much larger than for conventional cylinder piston arrangements. Even a comparably small pressure gradient generated by a miniaturized pump can overcome the friction force of the piston seal as the piston glides on the inner wall of the container.
In an especially advantageous approach the rigid container and movable piston are replaced by a flexible container. Such a flexible container may comprise, for example, two flexible wall sheets that are sealed together. Flexible containers have the advantage of a smaller volume surplus of the container in relation to its content, which reduces the manufacture costs and the achievable dimensions of an infusion pump device using such a flexible container. The volume of a flexible container for use in an infusion pump device in some embodiments may be up to 10 ml, in other embodiments 5 ml or less, and in still other embodiments 1.5 to 3.5 ml.
For use in an infusion pump device the flexible container must be connected to a conduit system of the device. For that purpose the flexible container may be provided with a port. Such a port can be mounted on the container with a flange sealed to a container wall sheet. US 2007/0049865 A1 discloses such a container. The port is provided with a septum, to be punctured by a hollow needle of the conduit system of the infusion pump device. Another possibility used for flexible containers are ports in the form of flexible tubes or rigid connection pieces welded between the two sheets of the container at the periphery of the flexible container. The fastening of the port to the container, for example, by gluing or welding, requires a precise production control to avoid high rejection rates, and furthermore limits the choice of suitable materials.
A common problem of flexible containers with ports as used, for example, in IV bags, is the dead volume resulting between the collapsed container and the port. Dead volume cannot be used, meaning that it cannot be emptied. Thus, flexible containers are impossible to completely drain. The resulting loss of useable container volume due to the dead volume is particularly high for smaller containers as they are suitable for infusion pumps having a total volume of only 5 mL or less. For single-use container filled with the medicament, the dead volume considerably increases the effective costs per dose and thus of the overall therapy costs, since a certain percentage of the medicament will inevitably remain in the container and has to be disposed. This cost effect is particularly important for expensive medicaments. In addition to the increased costs, the dead volume leads also to an increase of the overall volume of the flexible container, and thus of the volume of an infusion pump device comprising such a flexible container.
A further problem, particularly of flexible containers as they are known, is air remaining in the container. If, for example, a flexible container is provided empty, intended to be filled with the appropriate medicament by the user, the dead volume initially is filled with air. However, removing the air from flexible containers as they are known from the state of the art requires a certain skill of a user. If said air remains in the container, it may be administered instead of the liquid medicament, which leads to potentially dangerous dosing errors. Furthermore, the administration of air into a patient's body should be avoided for medical reasons.